Up-regulation of SEPT9_v1 stabilizes c-Jun-N-Terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells

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• 作者：Maria E. Gonzalez ; Olga Makarova ; Esther A. Peterson ; Lisa M. Privette ; Elizabeth M. Petty
• 关键词：JNK ; Septins ; Cell cycle regulation ; Cell proliferation ; Mammary epithelial cells ; Oncogenesis ; Cyclins
• 刊名：Cellular Signalling
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：21
• 期：4
• 页码：477-487
• 全文大小：1450 K

文摘

SEPT9_v1, the largest transcript of the septin gene family member, SEPT9, encodes a septin isoform implicated in the tumorigenic transformation of mammary epithelial cells. High levels of SEPT9_v1 expression also have been observed in both breast cancer cell lines, primary breast cancers as well as other solid tumor malignancies. We found a novel interaction between SEPT9_v1 and the c-Jun-N-terminal kinase (JNK), a mitogen-activated protein kinase important in cellular stress responses, cell proliferation, and cell survival. We found that up-regulation of SEPT9_v1 stabilizes JNK by delaying its degradation, thereby activating the JNK transcriptome. C-jun kinase assays in mammary epithelial cells expressing SEPT9_v1, compared to controls, exhibited increased JNK/c-Jun transcriptional activity. This increase was associated with increased levels of cyclin D1, a critical component of the proliferative response required for progression through G₁ of the cell cycle in many cell types. These findings demonstrate the first link between a septin protein and the JNK signaling pathway. Importantly, it suggests a novel functional role of SEPT9_v1 in driving cellular proliferation of mammary epithelial cells, a hallmark feature of oncogenesis that is directly relevant to breast cancer.